Genetic Variant NM_000240.4:c.1262+69A>G (chrX-43742116-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000240.4(MAOA):c.1262+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 16945 hom., 21101 hem., cov: 23)

Exomes 𝑓: 0.68 ( 171826 hom. 236366 hem. )

Failed GnomAD Quality Control

Consequence

MAOA
NM_000240.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.240

Publications

31 publications found

Variant links:

Genes affected

MAOA (HGNC:6833): (monoamine oxidase A) This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. Mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

MAOA Gene-Disease associations (from GenCC):

Brunner syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

MAOA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAOA	NM_000240.4 link	c.1262+69A>G		intron_variant	Intron 12 of 14	ENST00000338702.4	NP_000231.1	P21397-1Q53YE7Q49A63
MAOA	NM_001270458.2 link	c.863+69A>G		intron_variant	Intron 13 of 15		NP_001257387.1	P21397-2Q49A63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAOA	ENST00000338702.4 link	c.1262+69A>G		intron_variant	Intron 12 of 14	1	NM_000240.4	ENSP00000340684.3		P21397-1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

72236

AN:

110936

Hom.:

16951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.609

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.681

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.730

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.659

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.678

AC:

734750

AN:

1084239

Hom.:

171826

AF XY:

0.670

AC XY:

236366

AN XY:

353027

show subpopulations

African (AFR)

AF:

0.605

AC:

15879

AN:

26242

American (AMR)

AF:

0.675

AC:

22595

AN:

33468

Ashkenazi Jewish (ASJ)

AF:

0.715

AC:

13669

AN:

19125

East Asian (EAS)

AF:

0.430

AC:

12818

AN:

29804

South Asian (SAS)

AF:

0.414

AC:

21646

AN:

52281

European-Finnish (FIN)

AF:

0.624

AC:

24004

AN:

38455

Middle Eastern (MID)

AF:

0.708

AC:

2917

AN:

4120

European-Non Finnish (NFE)

AF:

0.708

AC:

590996

AN:

835136

Other (OTH)

AF:

0.663

AC:

30226

AN:

45608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

8456

16912

25368

33824

42280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17436

34872

52308

69744

87180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.651

AC:

72259

AN:

110989

Hom.:

16945

Cov.:

AF XY:

0.635

AC XY:

21101

AN XY:

33215

show subpopulations

African (AFR)

AF:

0.610

AC:

18582

AN:

30476

American (AMR)

AF:

0.680

AC:

7111

AN:

10462

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

1845

AN:

2633

East Asian (EAS)

AF:

0.426

AC:

1489

AN:

3492

South Asian (SAS)

AF:

0.382

AC:

1022

AN:

2675

European-Finnish (FIN)

AF:

0.610

AC:

3614

AN:

5923

Middle Eastern (MID)

AF:

0.737

AC:

157

AN:

213

European-Non Finnish (NFE)

AF:

0.700

AC:

37073

AN:

52936

Other (OTH)

AF:

0.655

AC:

988

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

909

1818

2727

3636

4545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.689

Hom.:

55450

Bravo

AF:

0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.035

(source)

DANN

Benign

0.62

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over